Applied Immune Technologies

www.tcrl.co.il
Haifa, Israel

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PubMed | Hillel Yaffe Medical Center, Pediatric Infectious Disease Unit and Clinical Microbiology Laboratory, Applied Immune Technologies, MeMed Diagnostics and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.


Bronner V.,Technion - Israel Institute of Technology | Denkberg G.,Applied Immune Technologies | Peled M.,Applied Immune Technologies | Elbaz Y.,Applied Immune Technologies | And 5 more authors.
Analytical Biochemistry | Year: 2010

Therapeutic monoclonal antibodies are becoming a significant and rapidly growing class of therapeutic pharmaceuticals. Their discovery and development requires fast and high-throughput methodologies for screening and selecting appropriate candidate antibodies having high affinity for the target as well as high specificity and low cross-reactivity. This study demonstrates the use of the ProteOn XPR36 protein interaction array system and its novel approach, termed One-Shot Kinetics, for the rapid screening and selection of high-affinity antibodies. This approach allows multiple quantitative protein binding analyses in parallel, providing association, dissociation, and affinity constants for several antibodies or supernatants simultaneously in one experiment. We show that the ProteOn XPR36 system is a valuable tool for use across multiple stages of the therapeutic antibody discovery and development process, enabling efficient and rapid screening after panning, affinity maturation, assay validation, and clone selection. © 2010 Elsevier Inc.


Oren R.,Technion - Israel Institute of Technology | Hod-Marco M.,Technion - Israel Institute of Technology | Haus-Cohen M.,Technion - Israel Institute of Technology | Thomas S.,University College London | And 8 more authors.
Journal of Immunology | Year: 2014

Adoptive transfer of Ag-specific T lymphocytes is an attractive form of immunotherapy for cancers. However, acquiring sufficient numbers of host-derived tumor-specific T lymphocytes by selection and expansion is challenging, as these cells may be rare or anergic. Using engineered T cells can overcome this difficulty. Such engineered cells can be generated using a chimeric Ag receptor based on common formats composed from Ag-recognition elements such as αβ-TCR genes with the desired specificity, or Ab variable domain fragments fused with T cell-signaling moieties. Combining these recognition elements are Abs that recognize peptide-MHC. Such TCR-like Abs mimic the fine specificity of TCRs and exhibit both the binding properties and kinetics of highaffinity Abs. In this study, we compared the functional properties of engineered T cells expressing a native low affinity αβ-TCR chains or high affinity TCR-like Ab-based CAR targeting the same specificity. We isolated high-affinity TCR-like Abs recognizing HLA-A2-WT1Db126 complexes and constructed CAR that was transduced into T cells. Comparative analysis revealed major differences in function and specificity of such CAR-T cells or native TCR toward the same antigenic complex. Whereas the native low-affinity αβ-TCR maintained potent cytotoxic activity and specificity, the high-affinity TCR-like Ab CAR exhibited reduced activity and loss of specificity. These results suggest an upper affinity threshold for TCR-based recognition to mediate effective functional outcomes of engineered T cells. The rational design of TCRs and TCR-based constructs may need to be optimized up to a given affinity threshold to achieve optimal T cell function. Copyright © 2014 by The American Association of Immunologists, Inc.


PubMed | Weizmann Institute of Science, Applied Immune Technologies, Technion - Israel Institute of Technology and University College London
Type: Comparative Study | Journal: Journal of immunology (Baltimore, Md. : 1950) | Year: 2014

Adoptive transfer of Ag-specific T lymphocytes is an attractive form of immunotherapy for cancers. However, acquiring sufficient numbers of host-derived tumor-specific T lymphocytes by selection and expansion is challenging, as these cells may be rare or anergic. Using engineered T cells can overcome this difficulty. Such engineered cells can be generated using a chimeric Ag receptor based on common formats composed from Ag-recognition elements such as -TCR genes with the desired specificity, or Ab variable domain fragments fused with T cell-signaling moieties. Combining these recognition elements are Abs that recognize peptide-MHC. Such TCR-like Abs mimic the fine specificity of TCRs and exhibit both the binding properties and kinetics of high-affinity Abs. In this study, we compared the functional properties of engineered T cells expressing a native low affinity -TCR chains or high affinity TCR-like Ab-based CAR targeting the same specificity. We isolated high-affinity TCR-like Abs recognizing HLA-A2-WT1Db126 complexes and constructed CAR that was transduced into T cells. Comparative analysis revealed major differences in function and specificity of such CAR-T cells or native TCR toward the same antigenic complex. Whereas the native low-affinity -TCR maintained potent cytotoxic activity and specificity, the high-affinity TCR-like Ab CAR exhibited reduced activity and loss of specificity. These results suggest an upper affinity threshold for TCR-based recognition to mediate effective functional outcomes of engineered T cells. The rational design of TCRs and TCR-based constructs may need to be optimized up to a given affinity threshold to achieve optimal T cell function.


Applied Immune Technologies | Entity website

EpiTarget is a unique approach for the discovery and validation of novel therapeutic MHC-based targets that can be applied to the isolation and characterization of new TCRL antibodies against a variety of disease-related intracellular targets. The EpiTarget approach combines bioinformatic analysis and mass spectroscopy strategies to identify target peptides presented on MHC molecules that are differentially expressed on diseased cells of various histological origins ...


Applied Immune Technologies | Entity website

Our immune system is composed of two arms: antibodies and T cells. Soluble antibody molecules can bind to cell surface expressed proteins with high affinity and specificity ...


Applied Immune Technologies | Entity website

AIT is actively seeking collaborations with bio-pharmaceutical companies specializing in antibody development. Our goals are to discover new disease-specific intracellular derived targets, and to co-develop TCRL antibodies for the treatment of cancer and viral diseases ...


Applied Immune Technologies | Entity website

January 2012,C.E ...


Applied Immune Technologies | Entity website

Applied Immune Technologies (AIT) is a drug development company specializing in T-Cell Receptor-Like (TCRL) antibodies for therapeutic and diagnostic applications in a variety of cancer, viral and autoimmune diseases, as well as identification and validation of novel therapeutic targets. From Target Discovery to Therapeutic Antibodies AIT's core technology platforms encompass the identification and validation of novel MHC-based targets, as well as development of therapeutic Human Recombinant T-Cell Receptor-Like (TCRL) antibodies with the unique ability to bind with these intracellular peptide/MHC complexes with the specificity of cytotoxic T-cell killer cells ...


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